Several potential mechanisms may explain this: alteration in HER2 dimers; activation of downstream signaling pathways such as PI3K/AKT, mTOR, and MAPK/ERK; and absence of downstream regulators or alternative transduction pathway from the insulin-like growth factor receptor (IGFR).130 In 2017, Deguchi et al.131 investigated HER2 expression and the occurrence of phosphatase and tensin homolog (PTEN) loss or PI3K mutation in 264 GC cases and reported the absence of PTEN in 34.5% of HER2-positive patients. The gene discussed is PTEN; the disease is gastric cancer.